The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 41, Issue 8
Displaying 1-24 of 24 articles from this issue
  • HERBERT IRSCHIK, WOLFRAM TROWITZSCH-KIENAST, KLAUS GERTH, GERHARD HOFL ...
    1988 Volume 41 Issue 8 Pages 993-998
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    A new natural saframycin was discovered in the culture broth of the myxobacterium, Myxococcus xanthus strain MX x48. The fermentation and isolation of the antibiotic are described. The name, saframycin Mx1, is proposed. The compound appears to interact with cellular DNA.
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  • TAXONOMY, FERMENTATION, ISOLATION, PHYSICO-CHEMICAL AND BIOLOGICAL CHARACTERISTICS AND STRUCTURE ASSIGNMENT
    HIROSHI HATANAKA, TORU KINO, MICHIZANE HASHIMOTO, YASUHISA TSURUMI, AK ...
    1988 Volume 41 Issue 8 Pages 999-1008
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    FR65814, a novel immunosuppressant, was isolated from the cultured broth of Penicillium jensenii F-2883. The structure was assigned to be 5, 6-dihydroxy-4-(l, 2-epoxy-1, 5-dimethyl-4-hexenyl)-1-oxaspiro[2, 5]octane by spectroscopic analyses. The compound suppressed the immune response at low concentration.
    In addition, a structually related component fumagillol, a known carcinolytic agent, was also isolated and found to show immunosuppressive activity.
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  • I. TAXONOMY, PRODUCTION, ISOLATION, PHYSICO-CHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITIES
    TAKAAKI AOYAGI, SHIGEMI YOSHIDA, SHIGEKO HARADA, AKIRA OKUYAMA, CHIEKO ...
    1988 Volume 41 Issue 8 Pages 1009-1014
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Benadrostin, a new inhibitor of poly(ADP-ribose) synthetase was discovered in the fermentation broth of Streptomyces flavovirens MH499-O'F1. It was purified by chromatography followed by solvent extraction and then isolated as colorless prisms. Benadrostin has the molecular formula of C8H5NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 34 μM.
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  • II. STRUCTURE DETERMINATION
    SHIGEMI YOSHIDA, HIROSHI NAGANAWA, TAKAAKI AOYAGI, TOMIO TAKEUCHI, HAM ...
    1988 Volume 41 Issue 8 Pages 1015-1018
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Benadrostin, a new inhibitor of poly(ADP-ribose) synthetase, has been isolated from the culture broth of Streptomyces flavovirens MH499-O'F1. The structure of benadrostin was defined as 8-hydroxy-2H-1, -benzoxazine-2, 4-dione by an analysis of spectral properties and chemical studies of benadrostin and its derivatives.
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  • SHUICHI GOMI, MASAJI SEZAKI, SHINICHI KONDO, TAKESHI HARA, HIROSHI NAG ...
    1988 Volume 41 Issue 8 Pages 1019-1028
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Structures of new antifungal antibiotics, benanomicins A and B were determined to be N-[[5-[6-deoxy-3-O-(β-D-xylopyranosyl)-β-D -galactopyranosyloxy]- 5, 6- dihydro-1, 6, 9, 14-tetrahydroxy-11-methoxy-3-methyl-8, 13-dioxobenzo[a]naphthacen-2-yl]carbonyl]-D-alanine and N-[[5-[4-amino-4, 6-dideoxy-3-O-(β-D-xylopyranosyl)-β-D-galactopyranosyloxy]-5, 6-dihydro1, 6, 9, 14-tetrahydroxy-1 1 -methoxy- 3 -methyl- 8, 13 -dioxobenzo[a]naphthacen-2-yl]carbonyI]-Dalanine, respectively, by spectral analyses and chemical degradation studies.
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  • G. MICHAEL BRIGHT, ARTHUR A. NAGEL, JON BORDNER, KISHOR A. DESAI, JOSE ...
    1988 Volume 41 Issue 8 Pages 1029-1047
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    A series of erythromycin A-derived semisynthetic antibiotics, featuring incorporation of a basic nitrogen atom into a ring expanded (15-membered) macrocyclic lactone, have been prepared and biologically evaluated. Semisynthetic modifications focused upon (1) varied substitution at the macrocyclic ring nitrogen and (2) epimerization or amine substitution at the C-4" hydroxyl site within the cladinose sugar. In general, the new azalides exhibit improved Gram-negative potency, expanding the spectrum of erythromycin A to fully include Haemophilus influenzae and Neisseria gonorrhoeae. When compared to erythromycin A, the azalides exhibit substantially increased half-life and area-under-the-curve values in all species studied. The overall in vitro/in vitro performance of N-methyl, C-4" epimers 3a and 9; and C-4" amine 11 identify these compounds as the most interesting erythromycin A-superior agents. Compound 3a has been advanced to clinical study.
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  • JEFFREY B. STEWART, VOLKER BORNEMANN, JIAN Lu CHEN, RICHARD E. MOORE, ...
    1988 Volume 41 Issue 8 Pages 1048-1056
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Tubercidin, toyocamycin, and the corresponding 5'-α-D-glucopyranose derivatives of the nucleosides are frequently responsible for much of the cytotoxicity and antimycotic activity associated with extracts of cultured cyanophytes belonging to the family Scytonemataceae. The 5'-α-D-glucopyranoses of tubercidin and toyocamycin, for example, are the major cytotoxic and fungicidal nucleosides in Fijian Plectonema radiosum and Hawaiian Tolypothrix tennis, respectively.
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  • 8. PURIFICATION AND CHARACTERIZATION OF 2-PHOSPHINOMETHYLMALIC ACID SYNTHASE FROM STREPTOMYCES HYGROSCOPICUS SF-1293
    KUMIKO W. SHIMOTOHNO, HARUO SETO, NOBORU OTAKE, SATOSHI IMAI, TAKESHI ...
    1988 Volume 41 Issue 8 Pages 1057-1065
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    2-Phosphinomethylmalic acid (PMM) synthase catalyzes the condensation of phosphinopyruvic acid (PPA), an analog of oxalacetic acid, and acetyl-CoA to form PMM. The enzyme was purified approximately 700-fold from a cell-free extract of Streptomyces hygroscopicus SF1293, a bialaphos producing organism, to an electrophoretically homogeneous state. The purified PMM synthase has a subunit molecular weight of 48, 000 by SDS-polyacrylamide gel electrophoresis and a native molecular weight of 90, 000 - 98, 000 by gel filtration. PMM synthase was relatively unstable, showed maximum activity at pH 8.0 and 30°C, and was inhibited strongly by p-chloromercuribenzoate, iodoacetamide and EDTA. Enzyme activity suppressed by EDTA was completely restored by adding Co+ + or Mn+ + and partially restored by addition of Ca+ +, Fe+ + or Mg+ +.
    The specific substrates of this enzyme are PPA or oxalacetic acid in addition to acetyl-CoA. The enzyme does not catalyze the liberation of Co A from acetyl-CoA in the presence of α-keto acids, such as pyruvate, α-ketoglutarate, deamino-α-ketodemethylphosphinothricin or phosphonopyruvate. The condensation reaction did not take place when propionyl-CoA or butyryl-CoA was used as a substrate in place of acetyl-CoA. The Km values of the enzyme were 0.05 mM for acetyl-CoA, 0.39 mM for PPA and 0.13 mM for oxalacetate. PMM synthase is very similar to (R)-citrate synthase of Clostridium in the inhibition pattern by sulfhydryl compounds, its metal ion requirement and stereospecificity; unlike CR)-citrate synthase PMM synthase was not inhibited by oxygen.
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  • TETRACENOMYCINS B3 AND D3, KEY INTERMEDIATES OF THE ELLORAMYCIN AND TETRACENOMYCIN C BIOSYNTHESIS
    JURGEN ROHR, SUSANNE EICK, AXEL ZEECK, PETER REUSCHENBACH, HANS ZÄ ...
    1988 Volume 41 Issue 8 Pages 1066-1073
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Tetracenomycins B3 and D3, besides tetracenomycin D (D1), were produced by a blocked mutant of the elloramycin producer Streptomyces olivaceus TÜ 2353. The compounds were isolated as red powders, and their structures were elucidated by comparing their physicochemical data with those of the known tetracenomycins A2, B1, B2, D and E. Tetracenomycin B3 (2), the main compound, and tetracenomycin D (3) were antibiotically inactive against Gram-positive and Gram-negative bacteria, whereas tetracenomycin D3 (1) showed a moderate activity against Bacillus subtilis and Arthrobacter aurescens. Tetracenomycin B3 (2) is the key intermediate where the biosynthesis of the elloramycins branches off from the line leading to tetracenomycin C (5) as the final product of the tetracenomycin biosynthesis branch.
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  • M. J. ALONSO, F. BERMEJO, A. REGLERO, J. M. FERNÁNDEZ-CAN&Oacut ...
    1988 Volume 41 Issue 8 Pages 1074-1084
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Different penicillins (phenylacetyl, 2-hydroxyphenylacetyl, 4-hydroxyphenylacetyl, phenoxyacetyl and 2-thiopheneacetylpenicillin) have been synthesized "in vitro" by direct N-acylation of 6-aminopenicillanic acid (6-APA) with the acyl group of several acyl-CoA derivatives. The enzyme that catalyzes these reactions, acyl-CoA: 6-APA acyltransferase of Penicillium chrysogenum, was purified to homogeneity (374-fold) and its amino acid composition is given. This protein accepts as substrates several aliphatic acids and different aromatic acids with the only requirement that an acetyl-CoA moiety must be present in the substrate molecule. Shortening or lengthening of the acyl moiety prevents the 6-APA-Nacylation reaction. The presence of an amino group in the α-position of the acetyl group does not allow this molecule to be used as substrate. However, different substitutions in the phenyl group (hydroxylation of the carbons 2 and 4) or its replacement by another aromatic ring (thiophene) were accepted with varying reactions rates in the acylation reaction when a 176-fold purified acyltransferase was employed. The homogeneity pure enzyme accepts as substrate thiophene acetyl-CoA but it did not 2-hydroxyphenyl and 4-hydroxyphenylacetyl-CoA. The presence of an oxygen atom between the aromatic and the acetyl moieties did not affect the catalysis.
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  • LA VERNE D. BOECK, DAVID S. FUKUDA, BERNARD J. ABBOTT, MANUEL DEBONO
    1988 Volume 41 Issue 8 Pages 1085-1092
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    A21978C, produced by Streptomyces roseosporus NRRL 11379, is an acidic lipopeptide antibiotic complex that inhibits Gram-positive bacteria. Individual factors of the complex possess an identical peptide core or "nucleus", and are differentiated by the distinctive fatty acid acyl group attached to the N-terminus of the nucleus. Certain members of the family Actinoplanaceae deacylated A21978C to yield the unaltered nucleus, which was then reacylated to form new analogs. Actinoplanes utahensis NRRL 12052 was the most efficient of these cultures, producing up to 500 μg of nucleus per ml of culture broth per hour, eacylation was also accomplished with semi-pure and tert-butoxycarbonyl (tert-RQC)-A21978C. In the latter, the ornithine amino group was blocked to prevent formation of diacyl analogs during reacylation. The acylase was an endoenzyme present in submerged cultures of A. utahensis from <18 to >168 hours of incubation. Whole cells suspended in phosphate buffer or entrapped in polyacrylamide gel also deacylated A21978C efficiently.
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  • MANUEL DEBONO, BERNARD J. ABBOTT, R. MICHAEL MOLLOY, DAVID S. FUKUDA, ...
    1988 Volume 41 Issue 8 Pages 1093-1105
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    The novel lipopeptide antibiotic A21978C complex is active against Gram-positive organisms. This complex consists of a common peptide nucleus with various lipid acyl groups at the TV-terminus characteristic of each individual factor. The fatty acid acyl group is removed by incubation of the A21978C complex with Actinoplanes utahensis to give the peptide nucleus. This peptide nucleus has the same amino acid sequence as A21978C. New analogs of A21978C were synthesized by acylation of the N-terminus of a ter/-butoxycarbonyl (tert-BOC)-protected nucleus and subsequent deprotection. 1H NMR showed that the newly introduced acyl group was at the desired TV-terminus. Three major groups of analogs were synthesized bearing fatty acid acyl, amino-aroyl and extended peptide side chains. Each analog was evaluated for antimicrobial activity and acute toxicity. Of these analogs, the w-decanoyl analog of A21978C (LY146032) gave the best survival in the mouse acute toxicity test at a high dose of 1, 000 mg/kg, iv and was chosen for further study. This analog has been named daptomycin.
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  • Kozo OCHI, YASUHISA TSURUMI, NOBUHARU SHIGEMATSU, MORITA IWAMI, KAZUYO ...
    1988 Volume 41 Issue 8 Pages 1106-1115
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Streptomyces griseoflavus, a bicozamycin-producing wild type strain and its highproducing one derived from it by multiple (>15) mutagenic treatments, were analyzed physiologically and biochemically. The high-producing strain was characterized by: (1) An increased pool size of amino acids including leucine and isoleucine, precursors for bicozamycin synthesis, (2) an earlier and greater accumulation of intracellular ppGpp, (3) a more accentuated decrease in GTP pool size, (4) a higher specific activity of ornithine transcarbamylase which produces citrulline, (5) an increased ability to form aerial mycelium, and (6) an increased resistance to its own antibiotic. We propose that (1), (2) and (4) may be responsible for the high yields of bicozamycin and, possibly, of some other antibiotics produced by Streptomyces sp.
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  • KUNIMOTO HOTTA, JUN ISHIKAWA
    1988 Volume 41 Issue 8 Pages 1116-1123
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    The streptomycin (SM) gene cluster was investigated for its distribution in streptomycetes by Southern hybridization using nick-translated DNA probes, which were isolated from the SM-6-phosphotransferase (SPH) and amidinotransferase (ADT) regions of the SM gene cluster of Streptomyces griseus SS-1198. BglII-digested genomic DNAs from SM-producing strains of S. griseus yielded the same size fragment (7.0 kb) which hybridized to both the SPH and ADT probes as expected from the restriction endonuclease cleavage map of the SM gene cluster. By contrast, no genomic DNA fragments from heterologous Streptomyces strains hybridized to the probes. Thus, only SM-producing strains of S. griseus possess the highly homologous SM gene cluster.
    Similarly, distribution of DNA sequences homologous to the kanamycin (KM)-resistance determinant (kan) from a KM-resistant regenerant of S. griseus SS-1198 protoplasts was also examined. Using the kan gene fragment as the probe it was revealed that the kan-related sequences are present in all the strains of S. griseus tested, irrespective of the type of antibiotics they produce. However, no hybridization to the kan gene probe (KAN) was observed with DNA digests derived from other Streptomyces species.
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  • KUNIKO NOMOTO, TAKAYOSHI OKABE, HIDEO SUZUKI, NOBUO TANAKA
    1988 Volume 41 Issue 8 Pages 1124-1129
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    Lactoquinomycin A (LQM-A), an antibiotic containing a quinone moiety in the molecule, inhibited biosyntheses of DNA, RNA and protein to a similar extent in doxorubicin-resistant mouse leukemia L5178Y cells at concentrations higher than 0.08μg/ml. The antibiotic caused cell death in a short period of incubation and the degree of cell death correlated with that of the inhibition of macromolecular syntheses, suggesting that the inhibition of macromolecular syntheses was not a primary effect of LQM-A. LQM-A served as a good electron acceptor, when cytochrome c reductase was used as a quinone reductase. The treatment of the cells with LQM-A significantly reduced cellular NADH and ATP levels. The generation of superoxide radical by LQM-A in cell lysate was observed by reduction of nitro blue tetrazolium, and the production of hydroxyl radical was confirmed by electron spin resonance. The importance of radical formation for the cytotoxicity of LQM-A is discussed.
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  • IN VITRO ACTIVITY AGAINST AEROBIC AND ANAEROBIC CLINICAL BACTERIAL ISOLATES
    BARBARA WEISSBERGER, GEORGE K. ABRUZZO, ROBERT A. FROMTLING, MARY E. V ...
    1988 Volume 41 Issue 8 Pages 1130-1136
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
    L-656, 575 (OCP-9-176) is a novel oxacephem superior to ceftazidime in in vitro activity against clinical isolates of Enterobacter species, methicillin-susceptibleStaphylococcus aureus and Staphylococcus epidermidis, and multiply-resistant Pseudomonas aeruginosa. Our results suggest that L-656, 575 has a high affinity for penicillin binding proteins of Pseudomonas and may bind preferentially to PBP-3 in this organism. L-656, 575 is active against β-Mactamase derepressed Enterobacteriaceae and ceftazidime-resistant P. aeruginosa.
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  • PHARMACOKINETICS AND EXPERIMENTAL CHEMOTHERAPY
    EVEMARIE C. GILFILLAN, BARBARA ANN PELAK, ROBERT A. FROMTLING, JUDITH ...
    1988 Volume 41 Issue 8 Pages 1137-1141
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
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    L-656, 575 is a new oxacephem that, based on studies in rhesus monkeys, is expected to have a moderately long half-life in humans. After administration of a 10-mg/kg dose by the intramuscular route to rhesus monkeys, peak serum concentrations of 32-54 μg/ml were seen at about 30 minutes, and the half-life was estimated to be 63 minutes. Urinary recovery of administered dose was >94% in 6 hours. In mice given a 20-mg/kg dose by the subcutaneous route, a peak serum concentration of 22.9 μg/ml was observed at 15 minutes after dosing, and the half-life in serum was about 18 minutes. Urinary recovery of the dose was 59 % in 6 hours. In another study in mice, administration of probenecid did not extend the half-life of L-656, 575, suggesting that the antibiotic is excreted primarily by glomerular filtration in this species. Binding to human plasma proteins was 30% at drug concentrations from 25 - 100 μg/ml. L-656, 575 also was shown to be efficacious in experimental bacteremias due to Gram-positive and Gram-negative pathogens in mice, thus confirming the broad spectrum of activity demonstrated for L-656, 575 in vitro.
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  • YOHJI EZURE, NOBUTOSHI OJIMA, KIYOTAKA KONNO, KATSUNORI MIYAZAKI, NAOY ...
    1988 Volume 41 Issue 8 Pages 1142-1144
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • HANSGEORG DELLWEG, JÜRGEN KURZ, WOLFGANG PFLÜGER, MICHAEL SC ...
    1988 Volume 41 Issue 8 Pages 1145-1147
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • RYUTARO IKEURA, SHIGEO MURAKAWA, AKIRA ENDO
    1988 Volume 41 Issue 8 Pages 1148-1150
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • ISAMI TAKAHASHI, KEI-ICHI TAKAHASHI, Kozo ASANO, ISAO KAWAMOTO, TOHRU ...
    1988 Volume 41 Issue 8 Pages 1151-1153
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • SEIJI SHIBAHARA, TSUNEO OKONOGI, YASUSHI MURAI, TOSHIAKI KUDO, TAKASHI ...
    1988 Volume 41 Issue 8 Pages 1154-1157
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • HARUO SETO, KAZUO FURIHATA, MUNEKI OHUCHI
    1988 Volume 41 Issue 8 Pages 1158-1160
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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  • M. JEERSANNIDHI THIRUMALACHAR, M. JEERSANNIDHI NARASIMHAN, Jr.
    1988 Volume 41 Issue 8 Pages 1161-1162
    Published: August 25, 1988
    Released on J-STAGE: April 19, 2006
    JOURNAL FREE ACCESS
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